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Figure 1: Impact on arterial wall condition of balance between shear stress-mediated endothelial nuclear factor kappa B-cell upregulation and nitric oxide synthesis

uptake, within 24 h, is secondary to macrophage uptake wall. [105] Therefore, the authors conclude that some of
and considering the crucial role of such inflammatory these identified genes may help identifying IAs at risk
cells in development and rupture of IAs, it indicates active of rupture, which warrant early treatment. [105]
inflammation in aneurysm walls of unstable aneurysm,
as suggested by one recent study. [102] These authors CONCLUSION
found that early ferumoxytol uptake was significantly
higher in aneurysms with marked upregulation of Aneurysm formation begins with a hemodynamically
inflammatory molecules such as cyclooxygenase-2 triggered endothelial inflammatory dysfunction, which
and microsomal prostaglandin E synthase-1 and is the cause rather than the consequence of aneurysms’
macrophages, independently from site and size of the development and rupture. The proinflammatory action
aneurysms. [101] Moreover, all three unruptured IAs of of shear stress prevails over its endothelium protective
their series with early ferumoxytol uptake that were action when the balance between NF-κB-mediated
managed conservatively ruptured less than 6 months production of NO and proinflammatory mediators (ROS,
after diagnosis, which supports the hypothesis that cytokines, adhesion molecules) shifts in favor of
inflammation is the cause but not the consequence inflammation because of alteration of the inhibitory
of the rupture. [102] Another line of research aiming at limb of the NO-mediated negative feedback on NF-κB
differentiating ruptured and unruptured IAs on the basis activation. Targets of the inflammatory reaction are,
of distinctive patterns of expression of inflammatory besides ECs, ECM, and VSMCs. Endothelial injury,
markers is the analysis of gene expression profile. [105] VSMCs phenotypic modulation with acquisition of
A recent study compared the gene expression arrays pro-inflammatory/pro-matrix remodeling properties
of ruptured and unruptured aneurysms and found a and subsequent Fas-mediated apoptotic cell death lead
significant difference of expression of genes encoding to the arterial wall weakening and aneurysm formation
macrophage-mediated inflammatory molecules and rupture. Clarifying the causative relationships that
according to the age of patients. [105] In particular, genes link hemodynamics, inflammation, vascular remodeling,
involved in vascular remodeling, inflammation, and and the development and rupture of IAs may provide
atherosclerosis such as S100/calgranulin genes (S100A8, effective tools to predict the individual risk of aneurysmal
S100A9, and S100A12), cluster of differentiation 163, rupture and aid the treatment decision-making process.
myeloperoxidase (MPO), were upregulated, while genes
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64 Neuroimmunol Neuroinflammation | Volume 2 | Issue 2 | April 15, 2015